In any neurological disease that results in cellular destruction, the proteins normally present within the cells will be released into the surrounding extracellular fluid. Some of these proteins have been shown to be unique to the nervous system and even to particular cell types of the nervous system. Preliminary animal and human studies have shown that after destructive lesions at least two of these proteins (14-3-2, a neuronal marker; and S-100, a glial marker) diffuse into cerebral spinal fluid and serum. Using sensitive radioimmunoassays (RIA) it has been possible to quantitate serum and CSF levels of these brain specific proteins after brain lesions. It is proposed to utilize changes in serum levels of these and other brain specific proteins as an aid in the clinical evaluation of patients with degenerative neurological disease. The procedure to be followed for the development of serum tests for individual brain proteins will be as follows: (1) Proteins shown to be brain specific are purified and specific antibodies prepared in rabbits (seven proteins have been taken to this stage - S-100, 14-3-2, 14-3-3, TC-1, AG-1, myelin basic protein and myelin proteolipid protein). (2) The proteins are localized using immunohistochemistry. (3) RIAs are developed. (4) Animal experiments are done to determine (a) if the antigens gain access to serum, (b) the factors that effect clearance from the serum and (c) the time course of appearance and clearance of the proteins after experimentally induced lesions. (5) Serum from control patients are examined for the presence of the proteins using RIA. (6) The levels of the proteins are determined by RIA in sequential sera from patients with active degenerative neurological disease. (7) The resulting serum data will be analyzed by comparison with the results of sequential neurological examinations, laboratory and radiological tests, pathology examination including autopsy data, and clinical course. The final aim will be to establish criteria by which the data on serum levels of various brain antigens can be interpreted to yield useful information regarding the differential diagnosis, the size of the lesion, the rate of progression, and the prognosis of the disease.